Hepatocyte canalicular transport of organic anions in bile duct-ligated rats

Transport of various intrinsic and extrinsic organic anions across the canalicular membrane of hepatocytes has been confirmed to occur via ATP-dependent primary active transport. To investigate these processes in the presence of obstructive jaundice, the uptake of radiolabeled taurocholate and pravastatin, a non-bile acid organic anion, by isolated hepatocyte canalicular membrane vesicles was observed after bile duct ligation in rats. The Mg++-ATPase and Na+, K+ -ATPase activity did not differ between membrane vesicle preparations from sham-operated and bile duct-ligated rats. Taurocholate uptake decreased significantly to 45% and 29%, while pravastatin uptake decreased to 35% and 35% of that in sham-operated rats at 2 and 7 days after bile duct ligation. These results indicate that the ATP-dependent transport systems for both bile salts and non-bile acid organic anions are impaired soon after the onset of obstructive jaundice.